Thermal Atropisomerism of Aglucovancomycin Derivatives:
Preparation of (<i>M</i>,<i>M</i>,<i>M</i>)- and (<i>P</i>,<i>M</i>,<i>M</i>)-Aglucovancomycins
Dale L. Boger
Susumu Miyazaki
Olivier Loiseleur
Richard T. Beresis
Steven L. Castle
Jason H. Wu
Qing Jin
10.1021/ja981928i.s002
https://acs.figshare.com/articles/journal_contribution/Thermal_Atropisomerism_of_Aglucovancomycin_Derivatives_Preparation_of_i_M_i_i_M_i_i_M_i_-_and_i_P_i_i_M_i_i_M_i_-Aglucovancomycins/3671355
The degradation of vancomycin to a series of aglucovancomycin derivatives containing modifications
in key functional groups and a study of their thermal atropisomerism are detailed. In all of the cases, selective
isomerism of the DE ring system atropisomers was observed under conditions where the CD and AB
stereochemistries were unaffected. Competitive retro aldol ring cleavage of the CD and DE ring systems (CD
> DE) was observed but could be minimized by the choice of solvent and thermal conditions (DE ring system)
or precluded by alcohol protection (CD ring system). Similarly, competitive main chain succinimide formation
through the loss of ammonia from the Asn residue could be minimized by the choice of thermal conditions or
prevented by carboxamide protection. Resynthesis of natural aglucovancomycin, (<i>M</i>,<i>M</i>,<i>M</i>)-<b>2</b>, and its unnatural
DE atropisomer (<i>P</i>,<i>M</i>,<i>M</i>)-<b>2</b> from <b>6</b> are described. The comparative antimicrobial activity of the key derivatives
and their unnatural DE ring system <i>P</i>-diastereomers are disclosed.
1998-08-22 00:00:00
chain succinimide formation
aldol ring cleavage
Asn residue
DE ring system atropisomers
carboxamide protection
CD ring system
AB stereochemistries
DE ring system
aglucovancomycin derivatives
DE ring system P
DE atropisomer
alcohol protection
DE ring systems
Thermal Atropisomerism
antimicrobial activity